PROJECT SUMMARY/ABSTRACT Ohio is experiencing one of the worst opioid injection epidemics in the country. The epidemic has severely affected rural Appalachian counties in southern Ohio, leading to a surge in overdose fatalities. Ohio?s heroin- related overdose rate is five times the national rate. In addition to overdose deaths, HCV has increased 400% between 2009-2013 and neonatal abstinence syndrome (NAS) has increased 9-fold between 2004-2014. Many evidence-based interventions (EBI), such as syringe service programs, medication-assisted treatment for substance use, naloxone provision for overdose treatment, and testing for HCV, HIV and sexually transmitted diseases (STD) are known to be effective in combating injection drug addiction and its consequences. Unfortunately, little is known about how to apply lessons learned in urban injection drug epidemics to sparsely- populated rural areas. In rural Ohio, as in much of the U.S., the delivery of EBI is limited or fragmented. A lack of coordination between key agencies to address overlap and gaps in services, especially in the context of severely constrained resources, has dire consequences for those struggling with opioid injection drug use. The proposed study will develop and implement a service delivery plan for EBI that can be scaled up in rural Ohio as well as other rural areas in the US experiencing opioid epidemics. In the UG3 phase, we will use a mixed methods approach to assess the socio-cultural and political context of the epidemic across multiple levels, including agencies, health care and service providers, and people who inject drugs (PWID) within three counties in rural Appalachia. We will use respondent-driven sampling (RDS) to assess injection behaviors and HCV, HIV, and STD prevalence. Building on this multi-level formative data, we will identify service gaps and work closely with key community stakeholders to build consensus around and prioritize the most relevant, feasible and acceptable implementation strategies to deliver EBI that may include coalition building, data synthesis across counties, crowdfunding models, and telemedicine. In the UH3 phase, we will implement, monitor and evaluate our service delivery plan for opioid injectors, using a regression point displacement design and repeat RDS surveys. Outcomes will include overdose deaths, NAS cases, HCV and HIV tests performed, and referral for HCV and HIV care. Implementation outcomes will include acceptability, adoption, feasibility, fidelity, penetration, sustainability, and cost. Scalability will be assessed by applying lessons learned in the UG3 phase in three additional counties during the UH3. Upon completion of the study, we will have enhanced EBI service delivery in multiple counties in Ohio and developed an exportable model of service needs assessment, community-engaged decision-making, and implementation. This model will be suitable for use throughout rural American in settings where opioid addiction has been identified and existing service delivery is limited or fragmented.